Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS)

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ClinicalTrials.gov Identifier: NCT00242944

Recruitment Status : Completed

First Posted : October 21, 2005

Last Update Posted : December 17, 2009

Sponsor:

Collaborators:

Yamaguchi University Hospital

Juntendo University

Information provided by:

Kyoto University

Study Description

Brief Summary:

The purpose of this study is to compare the effects of pitavastatin and atorvastatin on coronary plaque volume in patients with acute coronary syndrome and to clarify the relationship between coronary plaque volume, serum lipids, and inflammation markers in order to determine the significance of intensive lipid lowering therapy in patients with acute coronary syndrome in Japan.

Condition or disease	Intervention/treatment	Phase
Coronary Disease Hypercholesterolemia	Drug: Pitavastatin Drug: Atorvastatin	Phase 4

Detailed Description:

Previous mega trials have demonstrated that lipid lowering therapy with HMG-CoA reductase inhibitors (statins) reduces the incidence of major cardiovascular events by one-third, thus, the benefit of lipid lowering therapy has been substantiated. Such a benefit is significant especially for patients with coronary heart disease (CHD). The third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP-III) has suggested the advantage of more intensive lipid lowering therapy with a goal of reducing LDL-C below 70 mg/dL for such patients categorized as very high risk. In Japan, Japan Atherosclerosis Society (JAS) Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases 2002 have recommended that an LDL-C goal for patients with coronary heart disease should be below 100 mg/dL. However, there is no satisfactory evidence yet for the need to lower LDL-C level less than the goal prescribed in Japan.

Recently, research on diagnosis of coronary plaque has shown significant advances. The REVERSAL study in patients with a history of CHD, by diagnosis with intravascular ultrasound, suggested that intensive lipid lowering therapy with atorvastatin (80 mg/day) was associated with no growth of plaque (-0.4% compared to baseline), versus therapy with pravastatin (40 mg/day) which showed a slight increase (2.7%) in plaque volume over 18 months. In Japan, the ESTABLISH study, a single center study, indicated that early intensive lipid lowering therapy with atorvastatin (20 mg/day) could induce a significant reduction in plaque volume in patients with acute coronary syndrome. However, this benefit has not been verified in multicenter trials in Japan. Further, no comparative investigation into the effect of various concomitant drugs on coronary plaque has been done.

Pitavastatin is a chemically synthesized statin in Japan which has been marketed since late 2003. Pitavastatin has an LDL-C lowering effect as strong as atorvastatin and also has a superior HDL-C elevating effect; meanwhile, the effect of pitavastatin on coronary plaque has not been reported.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	307 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome
Study Start Date :	November 2005
Actual Primary Completion Date :	October 2007
Actual Study Completion Date :	March 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Atorvastatin Atorvastatin calcium Pitavastatin

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1 Pitavastatin	Drug: Pitavastatin Pitavastatin 4mg per day
Active Comparator: 2 Atorvastatin	Drug: Atorvastatin Atorvastatin 20mg per day

Outcome Measures

Primary Outcome Measures :

plaque volume [ Time Frame: one year ]

Secondary Outcome Measures :

total cholesterol (TC) [ Time Frame: one year ]
low-density lipoprotein (LDL)-cholesterol (LDL-C) [ Time Frame: one year ]
high-density lipoprotein (HDL)-cholesterol (HDL-C) [ Time Frame: one year ]
HDL2-C [ Time Frame: one year ]
HDL3-C [ Time Frame: one year ]
remnant like particles-cholesterol (RLP-C) [ Time Frame: one year ]
small dense LDL-C [ Time Frame: one year ]
non-HDL-C [ Time Frame: one year ]
LDL-C/HDL-C [ Time Frame: one year ]
apolipoprotein AI (apoA-I) [ Time Frame: one year ]
apoB [ Time Frame: one year ]
apoE [ Time Frame: one year ]
apoB/apoA-I [ Time Frame: one year ]
malondialdehyde-modified LDL (MDA-LDL) [ Time Frame: one year ]
phospholipids [ Time Frame: one year ]
lipoprotein(a) [Lp(a)] [ Time Frame: one year ]
high-sensitivity C-reactive protein (hs-CRP) [ Time Frame: one year ]
pentraxin 3 [ Time Frame: one year ]
leukocytes [ Time Frame: one year ]
coronary plaque area at culprit region [ Time Frame: one year ]
minimal lumen diameter (MLD) and percent (%) stenosis [ Time Frame: one year ]
major adverse cardiac events (cardiac death, Q or non-Q myocardial infarction and target vessel revascularization) [ Time Frame: one year ]
number of deaths from any cause [ Time Frame: one year ]
frequency of adverse drug reactions [ Time Frame: one year ]

Eligibility Criteria

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Ages Eligible for Study:	20 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with written consent by their own volition after being provided sufficient explanation for their participation in this clinical trial
Patients 20 years or older at the time of their consent
Patients with hypercholesterolemia as defined by any of the following criteria:
- TC >= 220 mg/dL;
- LDL-C >= 140 mg/dL;
- Cholesterol-lowering treatment is necessary in accordance with the investigator's judgement when LDL-C >= 100 mg/dL or TC >= 180 mg/dL.
Patients who have been diagnosed with acute coronary syndrome
Patients with successful percutaneous coronary intervention (PCI) by intravascular ultrasound (IVUS) guidance
Patients having coronary plaques (>= 500 µm in thickness or 20% or more in % plaque) at >= 5 mm from the previously treated area in the same branch of coronary artery

Exclusion Criteria:

Patients with bypass graft or in-stent restenosis at the site of PCI
Patients who had received PCI on the lesion in the past where the evaluation of coronary plaque volume is planned
Patients who had plaques in a non-culprit site and might receive PCI during the treatment period
Patients receiving lipid-lowering drugs (statins, fibrates, probucol, nicotinic acid or cholesterol absorption inhibitors)
Patients with familial hypercholesterolemia
Patients with cardiogenic shock
Patients receiving cyclosporine
Patients with any allergy to pitavastatin or atorvastatin
Patients with hepatobiliary disorders
Pregnant women, women suspected of being pregnant, or lactating women
Patients with renal disorders or undergoing dialysis
Patients who are ineligible in the opinion of the investigator

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00242944

Locations

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Japan
Juntendo University School of Medicine
Bunkyo-ku, Tokyo, Japan, 113-8421
Yamaguchi University Graduate School of Medicine
Ube, Yamaguchi, Japan, 755-8505
Kyoto University Graduate School of Medicine
Kyoto, Japan, 606-8507

Sponsors and Collaborators

Kyoto University

Yamaguchi University Hospital

Juntendo University

Investigators

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Study Chair:	Masunori Matsuzaki, MD, PhD	Professor of Medicine, Department of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine
Principal Investigator:	Hiroyuki Daida, MD	Professor of Medicine, Department of Cardiovascular Medicine, Juntendo University School of Medicine
Principal Investigator:	Takeshi Kimura, MD	Associate Professor of Medicine, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

More Information

Publications of Results:

Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M; JAPAN-ACS Investigators. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome] study). J Am Coll Cardiol. 2009 Jul 21;54(4):293-302. doi: 10.1016/j.jacc.2009.04.033.

Other Publications:

Miyauchi K, Kimura T, Morimoto T, Nakagawa Y, Yamagishi M, Ozaki Y, Hiro T, Daida H, Matsuzaki M. Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS): rationale and design. Circ J. 2006 Dec;70(12):1624-8. Erratum in: Circ J. 2007 Jan;71(1):172.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fukushima Y, Daida H, Morimoto T, Kasai T, Miyauchi K, Yamagishi S, Takeuchi M, Hiro T, Kimura T, Nakagawa Y, Yamagishi M, Ozaki Y, Matsuzaki M; JAPAN-ACS Investigators. Relationship between advanced glycation end products and plaque progression in patients with acute coronary syndrome: the JAPAN-ACS sub-study. Cardiovasc Diabetol. 2013 Jan 7;12:5. doi: 10.1186/1475-2840-12-5.

Takashima H, Ozaki Y, Morimoto T, Kimura T, Hiro T, Miyauchi K, Nakagawa Y, Yamagishi M, Daida H, Mizuno T, Asai K, Kuroda Y, Kosaka T, Kuhara Y, Kurita A, Maeda K, Amano T, Matsuzaki M; JAPAN-ACS Investigators. Clustering of metabolic syndrome components attenuates coronary plaque regression during intensive statin therapy in patients with acute coronary syndrome: the JAPAN-ACS subanalysis study. Circ J. 2012;76(12):2840-7. Epub 2012 Sep 7.

Ohashi T, Shibata R, Morimoto T, Kanashiro M, Ishii H, Ichimiya S, Hiro T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura T, Daida H, Murohara T, Matsuzaki M. Correlation between circulating adiponectin levels and coronary plaque regression during aggressive lipid-lowering therapy in patients with acute coronary syndrome: subgroup analysis of JAPAN-ACS study. Atherosclerosis. 2010 Sep;212(1):237-42. doi: 10.1016/j.atherosclerosis.2010.05.005. Epub 2010 May 11.

Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M; JAPAN-ACS Investigators. Diabetes mellitus is a major negative determinant of coronary plaque regression during statin therapy in patients with acute coronary syndrome--serial intravascular ultrasound observations from the Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome Trial (the JAPAN-ACS Trial). Circ J. 2010 Jun;74(6):1165-74. Epub 2010 May 12.

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Responsible Party:	Masunori Matsuzaki, Yamaguchi University Graduate School of Medicine
ClinicalTrials.gov Identifier:	NCT00242944
Other Study ID Numbers:	H17-49
First Posted:	October 21, 2005 Key Record Dates
Last Update Posted:	December 17, 2009
Last Verified:	June 2008

Keywords provided by Kyoto University:


Acute coronary syndrome Hypercholesterolemia Primary coronary intervention Hydroxymethylglutaryl-CoA reductase inhibitors	coronary plaque Angioplasty, Transluminal, Percutaneous Coronary Ultrasonography, Interventional

Additional relevant MeSH terms:

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Acute Coronary Syndrome Coronary Disease Hypercholesterolemia Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders	Metabolic Diseases Atorvastatin Pitavastatin Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors

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